The guaianolides, pseudoguaianolides and tiglane diterpenes are members of a class of natural products which possess a bicyclo[5.3.0]decane skeleton. These functionally and stereochemically complex natural products have exhibited a broad and potent spectrum of biological activities, including antitumor, cytotoxic, antineoplastic and antileukemic activities, as well as allergenic, antihelminthic, antifeedant, contraceptive, cocarcinogenic and molluscicidal properties. As a result of these activities and the small quantities of materials available from plant sources, these compounds have been the targets of total chemical syntheses. This proposal describes methodology which should allow the synthesis of highly oxygenated powerfully active members of the guaianolide and pseudoguaianolide (ambrosanolide and helenanolide) families of sesquiterpenes. Central to this approach is the use of a furyl residue as a butyrolactone equivalent which will impart regiochemical control in annulation processes. The introduction of an intact furyl unit into a guaiane, pseudoguaiane or tiglane intermediate should allow routine control of stereochemistry in the normally flexible seven-membered B-ring. The methodology developed as well as the control of stereochemistry should be applicable to the synthesis of other bicyclo[5.3.0]decane containing compounds such as the tiglanes, daphnanes and ingenanes.